| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2015: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2014: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2013: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Outline of Final Research Achievements |
We evaluated the efficacy of metformin (Met) and 5-FU combined therapy against human oral squamous cell carcinoma (OSCC). MTT assay and TUNEL assay revealed that Met (4 mg/ml) and 5-FU (2.5 μg/ml) combination treatment effectively inhibited cell growth and induced apoptosis in OSCC cell lines compared to either agent alone. Lactate colorimetric assay detected decreased level of lactate in the supernatants of Met and 5-FU treated cells compared to cells treated with Met or 5-FU. Western blot analysis showed down-regulation of HIF-1α and mTOR expression, and up-regulation of AMPKα in cells treated with Met and 5-FU combination treatment. Combination therapy with Met (200 mg/kg, i.p.) and 5-FU (10 mg/kg, i.p.) for 4 weeks effectively reduced tumor growth (77.6%) compared to Met (59.9%) or 5-FU (52%) alone in nude mice. These findings suggest that Met and 5-FU combined therapy could exert strong antitumor effect against OSCC through the inhibition of Warburg effects.
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